POS1014 IMPACT OF SERUM INTERLEUKIN 22 AS A BIOMARKER FOR THE DIFFERENTIAL USE OF MOLECULAR TARGETED DRUGS FOR PSORIATIC ARTHRITIS
Authors: I. Miyagawa, S. Nakayamada, M. Ueno, Y. Miyazaki, Y. Tanaka
Journal: Annals of the Rheumatic Diseases (2022)

Background Although each bDMARD target different molecules, no optimal drug selection method has been established. Because studies directly comparing TNF-i and IL-17-i have shown that these drugs are equally effective, the establishment of an optimal selection method for these drugs can contribute to better patient outcomes. We reported the possibility of stratification of patients by peripheral blood lymphocytes phenotyping and precision medicine based on the selective use of bDMARDs in psoriatic arthritis (PsA). However, since peripheral blood lymphocytes phenotyping is complex, the development of simple methods using biomarkers to stratify patients and simple treatment strategies based on such methods is needed to promote precision medicine in a real-world clinical setting. Objectives We explored whether serum cytokines could be used as biomarkers for optimal use TNF-i and IL-17-i in patients with PsA. Methods In cohort 1 (IL-17-i [n=23] or TNF-i [n=24] for ≥1 year), we identified serum cytokines that predicted the achievement of DAPSA remission (REM), PASI 90 and Minimal Disease Activity after 1 year of TNF-i or IL-17-i therapy. Subsequently, we developed treatment strategies based on the identified cytokines. In cohort 2, treatment responses were compared between the strategic treatment group (n=17), which was treated based on the treatment strategies, and the mismatched treatment group (n=17) to verify the validity of the treatment strategies developed using serum cytokines as biomarkers. Results In cohort 1, serum IL-22 concentrations were statistically identified as a predictor of DAPSA remission after 1 year of IL-17-i therapy. However, no baseline serum cytokines were identified as factors contributing to achievement of DAPSA-REM in the TNF-i-treated group or achievement of PASI90 and Minimal Disease Activity in either group. Using a cut-off value of 0.61376 (sensitivity, 81.8%; specificity, 91.7%; area under the curve, 0.848) determined by a ROC analysis, we stratified 47 patients into the IL-22 high group (n=25) (0.61376&lt;) and the IL-22 low group (n=22) (&lt; 0.61376). Serum IL-17 concentrations were significantly higher in both the IL-22 high and IL-22 low groups than in the healthy control (HC), whereas no significant difference was observed between the IL-22 high and IL-22 low groups. The serum TNF-α concentrations did not significantly differ between the IL-22 low and HC; however, they were significantly higher in the IL-22 high group than in the HC and IL-22 low groups. Based on these results, we created treatment strategies using TNF-i and IL-17-i based on serum IL-22 concentrations, that is, initiation of IL-17-i therapy in patients with low IL-22 concentrations and TNF-i therapy in patients with high IL-22 concentrations. To validate the efficacy of the treatment strategies, we retrospectively compared the efficacy of the bDMARDs at 1 year between the following groups in cohort 2. The strategic treatment group (n=17) included patients with low IL-22 concentrations who were treated with IL-17-i and those with high IL-22 concentrations who were treated with TNF-i. The mismatched treatment group (n=17) included patients with low IL-22 concentrations who were treated with TNF-i and those with high IL-22 concentrations who were treated with IL-17-i. No statistically significant differences were observed between the two groups in baseline characteristics at the initiation of bDMARD. After initiation of bDMARD, tender joint counts, swollen joint counts, CRP, DAPSA, and PASI were significantly improved in both groups. When the treatment responses over 1 year were compared between the two groups, the rate of achieving DAPSA-REM (58.8% vs. 25.3%, P=0.0399) and Minimal Disease Activity (82.3% vs. 41.2%, P=0.0162) at M12 was significantly higher in the strategic treatment group. There were no statistically significant differences in the rates of achieving PASI75 or PASI90 at M 6 or 12. Conclusion We verified that serum IL-22 can be used as a simple biomarker for the proper selection of TNF-i and IL-17-i. Acknowledgements The authors thank the study participants, without whom this study could not have been accomplished, and all medical staff at all participating institutions for providing the data, especially Ms. Hiroko Yoshida, Ms. Youko Saitou, Ms. Machiko Mitsuiki and Ms. Ayumi Maruyama for the excellent data management. The authors thank Ms. M. Hirahara for providing excellent technical assistance. We also thank Dr Kazuyoshi Saito at Tobata General Hospital; Dr Kentaro Hanami and Dr Shunsuke Fukuyo at Wakamatsu Hospital of the University of Occupational and Environmental Health; Dr Keisuke Nakatsuka at Fukuoka Yutaka Hospital, and all staff members at Kitakyushu General Hospital and Shimonoseki Saiseikai Hospital. Nakama Municipal Hospital, and Steel Memorial Yawata Hospital for their engagement in data collection. Disclosure of Interests Ippei Miyagawa: None declared, Shingo Nakayamada Speakers bureau: consulting fees, speaking fees, and/or honoraria from Bristol-Myers, Pfizer, GlaxoSmithKline, Sanofi, Astellas, Asahi-kasei, and Boehringer Ingelheim and research grants from Mitsubishi-Tanabe and Novartis., Masanobu Ueno: None declared, Yusuke Miyazaki: None declared, Yoshiya Tanaka Speakers bureau: speaking fees and/or honoraria from Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, and Janssen, Consultant of: consultant fees from Eli Lilly, Daiichi-Sankyo, Taisho, Ayumi, Sanofi, GSK, and Abbvie., Grant/research support from: research grants from Abbvie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, and Daiichi-Sankyo